Research Selection
Based on the previous search strategy, 434 studies were searched from the online database. After deleting duplicate records, a total of 291 records were retained. 14[1-14]studies were eventually collated(see Fig. 1), comprising 9 case reports, 1 case series report, 4 cohort studies. Among them, 11 were English articles, and 3 were Chinese articles.
Assessment of risk of bias of included studies
Four studies[6,7,12,13] are cohort studies reporting on cases of infants born to SARS-CoV-2-infected mothers, in which 3 / 1 / 1 / 3 newborns were positive for SARS-CoV-2 real-time polymerase chain reaction (SARS-CoV-2-PCR), which are regarded as case reports. Article [9] is a case series report (4 cases). The case series study quality evaluation tool (IHE)[15] was used to evaluate the bias risk. IHE include 20 items, which are answered with "yes", "no" and "unclear", respectively. If the answer is "yes", the entry is judged to be "1" score, and items that meet more than 14 (70%) are acceptable bias risk. Table 1 shows that the literature [9] satisfies 14 (70%) items, which is an acceptable bias risk(Table S1).
Characteristics of included human studies and overview of findings
A total of 21 neonatal cases of COVID-19 have been reported in 14 studies. Repeated cases in these studies are as follows: the first repeated case is in the study [1] and study [9], the third repeated case is in the study [3] and study [9], the sixth repeated case is in the study [6] and study [12]. Finally, 18 cases of COVID-19 were included in this analysis.
The 18 newborns were from China (9 cases, 50%), Italy (4 cases, 22%), Spain (1), Iran (1), South Korea (1), Peru (1), and the United States (1). All newborns were positive for the SARS-CoV-2-PCR. As table 1 shows, the second newborn is the earliest infected patient who was diagnosed with SARS-CoV-2 infection on February 4, 2020. The youngest infant was the 14th newborn from Peru, who was diagnosed with SARS-CoV-2 infection only 16 hours after birth. Of these 18 cases, 6 had a clear history of contacting SARS-CoV-2 infected patients in their families, and 10 were isolated immediately after birth, because their mothers were diagnosed or suspected with COVID-19. As to the 10th and 18th cases, because their family members were not tested for SARS-CoV-2 nucleic acid, it was not possible to determine whether they had a history of contacting with SARS-CoV-2 infection(Table 1).
General information and clinical features of 18 newborns
Gestational age was described in 11 articles, patient 8 and 14 were premature infants, who underwent urgency cesarean because their mothers were confirmed with maternal COVID-19 pneumonia. The delivery of 15 newborns was reported, of whom 12 were born by cesarean and 3 by vaginal delivery. Three newborns were breastfed and more were fed with formula milk. There were 13 males (86.7%) and 2 females (13.3%), the gender of patient 14, 15, 16 were not described. The mothers of patient 4, 6, 7, 8, 11, 12, 14, 15, 16 and 17 were all suspected or diagnosed with COVID-19, so they were isolated immediately after birth.
Sixteen newborns’ clinical manifestations were reported. The most common clinical manifestations were fever (62.5%), shortness of breath (50.0%), diarrhea/vomiting/feeding intolerance(43.8%), cough (37.5%), dyspnea (25.0%), and nasal congestion/runny nose/sneeze(25.0%). Atypical symptoms included jaundice and convulsion. Patient 2 had vomiting and milk refusal as the first symptom, patient 5 was admitted to hospital with fever and convulsion as the first manifestation. Patient 6 and 9 did not have any obvious clinical symptoms, but the nucleic acid tests were positive. Among the 16 newborns, there were 6 severe cases (37.5%), and three of them had complications. Patient 3 showed atrial septal defect (6.9mm) by echocardiography and was complicated with cardiac insufficiency. Patient 8 underwent neonatal resuscitation at birth with neonatal respiratory distress syndrome(NRDS) and neonatal early-onset septicemia, and patient 18 was complicated with pneumothorax(Table 2).
Laboratory examination and imaging findings of 18 newborns
Table 3 shows that blood routine were described in 11 cases, including case 1, 2, 3, 6, 7, 8, 10, 13, 18, with white blood cell(WBC) fluctuating between 4.51~20.4(×10^9/L ), lymphocyte(L) number decreased in case 4, 7, 8, 10, 18. Patient 3 was reported with anemia with a hemoglobin of 85(g/L). Thrombocytopenia had been reported in patient 2 and 8. Fortunately, all of these cases were normal when reexaminating during hospitalization. C-reactive protein(CRP) and procalcitonin(PCT) increased significantly in the 18th case. The liver function was abnormal in the 4th case, which showed slight increase of transaminase and serum total bilirubin, and no renal function impairment was found in all reports. The laboratory examinations of patient 3, 4, 5, 7 showed myocardial function damage, patient 3 showed an increase in N-Terminal pro-brain natriuretic peptide(NT-proBNP) , patient 4 showed an increase in creatine kinase(CK), patient 5 showed an increase in serum creatine kinase and lactate dehydrogenase(LDH), and patient 7 showed an increase in the level of creatine kinase isoenzymes (CK-MB) .
Nasopharyngeal swabs were positive for SARS-CoV-2 in all newborns, and anal swabs was performed in 8 newborns, of which 7 were positive.
Imaging examinations were mentioned in 10 cases. Chest X-ray of Patient 1, 2, 3, 4, 6, 7, 8, 18 showed pneumonia, and other abnormal chest radiograph appearances including neonatal respiratory distress syndrome in case 8 and unilateral lesions and pneumothorax in case 18. Six newborns had computed tomography(CT) examination, 3 cases had positive appearances. Patient 1 showed small strip blurred shadow scattered in both lung fields, patient 3 showed patchy high-density and adjacent pleural thickening, and patient 4 showed high-density nodular shadow under the pleura of the posterior segment of the upper lobe of the right lung(Table 3).
Treatment and clinical outcomes of 18 newborns
Table 4 shows that 6 cases were treated with antibiotics (6/12), 3 studies mentioned antiviral therapy, including interferon, ribavirin, lopinavir / ritonavir, and oseltamivir. 4 infants needed oxygen therapy, patient 2 needed non-invasive ventilation, and patient 14 received invasive ventilation and non-invasive ventilation for respiratory support. Seven newborns were mentioned of time that the nucleic acid test turned negative, the longest time was 21 days. The longest hospital duration was in the case 3, who was in hospital for 30 days. All newborns recovered and discharged from hospital, and there was no death.